Body composition and inflammation variables as the potential prognostic factors in epithelial ovarian cancer treated with Olaparib.

Background: Epithelial ovarian cancer (EOC) is a significant cause of mortality among gynecological cancers. While Olaparib, a PARP inhibitor, has demonstrated efficacy in EOC maintenance therapy, individual responses vary. This study aims to assess the prognostic significance of body composition and systemic inflammation markers in EOC patients undergoing initial Olaparib treatment. Methods: A retrospective analysis was conducted on 133 EOC patients initiating Olaparib therapy. Progression-free survival (PFS) was assessed through Kaplan-Meier analysis and Cox proportional hazards regression. Pre-treatment computed tomography images were utilized to evaluate body composition parameters including subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), skeletal muscle area index (SMI), and body mineral density (BMD). Inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum albumin, and hemoglobin levels, were also measured. Results: The median follow-up duration was 16 months (range: 5-49 months). Survival analysis indicated that high SATI, high VATI, high SMI, high BMD, low NLR, and low PLR were associated with decreased risk of disease progression (all p < 0.05). Multivariate analysis identified several factors independently associated with poor PFS, including second or further lines of therapy (HR = 2.16; 95% CI = 1.09-4.27, p = 0.027), low VATI (HR = 3.79; 95% CI = 1.48-9.70, p = 0.005), low SMI (HR = 2.52; 95% CI = 1.11-5.72, p = 0.027), low BMD (HR = 2.36; 95% CI = 1.22-4.54, p = 0.010), and high NLR (HR = 0.31; 95% CI = 0.14-0.69, p = 0.004). Subgroup analysis in serous adenocarcinoma patients revealed distinct prognostic capabilities of SATI, VATI, SMI, PLR, and NLR. Conclusion: Body composition and inflammation variables hold promise as predictors of therapeutic response to Olaparib in EOC patients. Understanding their prognostic significance could facilitate tailored treatment strategies, potentially improving patient outcomes.

Radiogenomic analysis based on lipid metabolism-related subset for non-invasive prediction for prognosis of renal clear cell carcinoma.

PURPOSE: Multiple lipid metabolism pathways alterations are associated with clear cell renal cell carcinoma (ccRCC) development and aggressiveness. In this study, we aim to develop a novel radiogenomics signature based on lipid metabolism-related genes (LMRGs) that may accurately predict ccRCC patients' survival. MATERIALS AND METHODS: First, 327 ccRCC were used to screen survival-related LMRGs and construct a gene signature based on The Cancer Genome Atlas (TCGA) database. Then, 182 ccRCC were analyzed to establish radiogenomics signature linking LMRGs signature to radiomic features in The Cancer Imaging Archive (TCIA) database included enhanced CT images and transcriptome sequencing data. Lastly, we validated the prognostic power of the identified radiogenomics signature using these patients of TCIA and the Third Xiangya Hospital. RESULTS: We identified the LMRGs signature, consisting of 13 genes, which could efficiently discriminate between low-risk and high-risk patients and serve as an independent and reliable predictor of overall survival (OS). Radiogenomics signature, comprised of 9 radiomic features, was created and could accurately predict the expression level of LMRGs signature (low- or high-risk) for patients. The predictive performance of this radiogenomics signature was demonstrated through AUC values of 0.75 and 0.74 for the training and validation sets (at a ratio of 7:3), respectively. Radiogenomics signature was proven to be an independent risk factor for OS by multivariable analysis (HR = 4.98, 95 % CI:1.72-14.43, P = 0.003). CONCLUSIONS: The LMRGs radiogenomics signature could serve as a novel prognostic predictor.

Hypso- or bathochromic phosphorescent mechanochromic mononuclear Cu(I) complexes with a bis(2-diphenylphosphinophenyl)ether auxiliary ligand.

Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.

Human endoderm stem cells reverse inflammation-related acute liver failure through cystatin SN-mediated inhibition of interferon signaling.

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.

Anti-corrosion and self-healing coatings with polyaniline/epoxy copolymer-urea-formaldehyde microcapsules for rusty steel sheets.

Polyaniline (PANI)/Epoxy copolymer as a core material was synthesized via a chemical oxidation method. Various analytical techniques, including scanning electron microscope, Fourier transform infrared spectroscopy, energy dispersive spectroscopy, thermogravimetry, and electrochemical impedance spectroscopy, were used to characterize the morphology, compositions, and self-healing and anticorrosion properties of the prepared microcapsules and coatings. The prepared PANI/Epoxy copolymer showed the best electrochemical corrosion resistance when the ratio of PANI to epoxy was 0.05: 1 (wt.:wt.). For the mass fraction of the core (PANI/Epoxy copolymer) of 60.84 ± 0.06 wt%, the mean particle diameter of the prepared microcapsules was 4.20 ± 0.92 µm. The coatings with 15 wt% microcapsules possessed excellent self-healing performance and corrosion resistance. The low-frequency impedance modulus at 0.01 Hz of scratched coatings immersed in the NaCl solution for 24 h was 5.27 × 106 Ω·cm2. Scratched self-repairing coating samples were able to resist corrosion for 384 h; thus, the microcapsules can be used to significantly extend the service life of the coatings. Microcapsule-containing PANI/Epoxy copolymers are expected to find use in anticorrosion coating systems, where the coatings could be applied directly on rusty steel surfaces.

An ICT-based fluorescence enhancement probe for detection of Sn2+ in cancer cells.

Development of a novel fluorescence enhancement probe for detection of Sn2+ in organisms, with high selectivity and sensitivity, is of great interest but remains a great challenge. Herein, an ICT-based fluorescence probe TPPB was rationally developed to act as an 'enhancement' luminescent and "naked-eye" indicator for Sn2+ detection. Importantly, spectroscopic studies indicated that TPPB was a fluorescence enhancement sensor for Sn2+ with rapid response, low detection limit (0.116 µM) and excellent binding constant (1.6 × 104 M-1). The mechanism of TPPB response to Sn2+ was further proved by 1H NMR titration, and enhancement calculations. Furthermore, TPPB is applied as a fluorescence probe for imaging in Hela cells, indicated that it can be potentially applied for Sn2+ sensing in biological fields.

Ice-interface assisted large-scale preparation of polypyrrole/graphene oxide films for all-solid-state supercapacitors.

In this paper, large-scale, self-standing polypyrrole/graphene oxide (PPy/GO) nanocomposite films were prepared by an environmentally friendly and easy-to-operate confined polymerization method, and were also assembled as electrode materials for symmetric all-solid-state supercapacitors. In this paper, large-scale, self-standing polypyrrole/graphene oxide (PPy/GO) nanocomposite films were prepared by an environmentally friendly and easy-to-operate confined polymerization method, and were also assembled as electrode materials for symmetric all-solid-state supercapacitors. The morphology, chemical structure and electrochemical property were characterized by field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FTIR), cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS), respectively. The lamellar structure of GO and both strong interaction with ice and pyrrole could promote polymerization of pyrrole and improve the compactness of the film. With the aid of GO, the conjugation length of PPy increased, the resistance of the material decreased, and the electrochemical energy storage of the composite film was significantly enhanced. In the case of 2.5 wt% GO, the prepared PPy/GO nanocomposite supercapacitor exhibited a high area specific capacitance of 97.3 mF cm-2 at 1 mA cm-2. Furthermore, the PPy/GO film supercapacitor also showed excellent cycling stability and good flexibility.

Protection of Mild Steel by Waterborne Epoxy Coatings Incorporation of Polypyrrole Nanowires/Graphene Nanocomposites.

Polypyrrole nanowires/graphene (PPyNG) nanocomposites as anticorrosive fillers were prepared by in situ polymerization in order to improve the anticorrosion performance of waterborne epoxy coatings. Field emission scanning electron microscope (FESEM) and Fourier transform infrared spectroscopy (FTIR) characterized the morphologies and structures of the synthesized PPyNG. The polypyrrole nanowires with about 50 nm in diameter were obtained. Conjugation length of PPy was increased with the addition of graphene. Open circuit potential (OCP) measurements, Tafel polarization curves, and electrochemical impedance spectroscopy (EIS) using an electrochemical workstation evaluated the anticorrosion properties of the waterborne epoxy/PPyNG coatings (EPPyNG). The studied nanocomposite coating possessed superior corrosion protection performance when the graphene content of the filler was 2 wt %. Its corrosion rate was about 100 times lower than that of neat epoxy coating. The higher barrier properties of nanocomposite coating and passivation effect of polypyrrole nanowires were beneficial in corrosion protection.

Preparation of nanocellulose and its potential in reinforced composites: A review.

Cellulose is a kind of natural polymer material, which is composed of bundle-like fibrils. By peeling the fibrils layer by layer, the size of cellulose can be nanocrystallized, and nanofibers and nanocrystals with unique and potentially useful features can be prepared. As an emerging functional polymer material, nanocellulose has become a research hotspot in the field of technology. This review discusses the preparation of nanocellulose, including the commonly used hydrolysis, oxidation, physical and environmentally friendly ionic liquid methods. The advantages and disadvantages of different methods are also compared. And the review introduced the application of nanofiberized cellulose and nanocellulose crystals in the fields of thermosetting and thermoplastics, such as polylactic acid, polypropylene, epoxy resin and so on. The critical factors in the manufacturing of nanocellulose composites and mechanical properties are discussed to provide a reference for the further application and development of nanocellulose.

MMP8 and MMP9 gene polymorphisms were associated with breast cancer risk in a Chinese Han population.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that can breakdown almost all extracellular matrix components. MMP8 and MMP9 have been shown to be associated with breast cancer (BC) risk in European and American populations. However, few studies have focused on the polymorphisms of MMP8 and MMP9 in Chinese Han BC patients. We investigated nine single nucleotide polymorphisms (SNPs) in 571 BC cases and 578 controls to evaluating their association with risk of BC. The frequency of the "A" allele of rs3787268 was significantly lower in BC cases than in controls (P = 0.025). In the genetic model analysis, the minor allele "T" of rs11225394 in MMP8 was associated with increased risk of BC under the recessive model (P = 0.019), and the minor allele "A" of rs3787268 was associated with decreased risk of BC under the dominant model (P = 0.014). Additionally, the haplotype "AGTCA" constructed by rs3740938, rs2012390, rs1940475, rs11225394, and rs11225395 and the haplotype "CCG" constructed by rs3918249, rs3918254 and rs3787268 were associated with increased risk of BC (P < 0.05). Our data showed that polymorphisms of MMP8 and MMP9 may be associated with BC risk in the Chinese Han population.

Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide-hydrazone and carboxamide moiety.

A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50 values of 2.21µg/mL, 1.67µg/mL and 1.11µg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide-hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest.

Synthesis and antifungal activity of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives as pyruvate dehydrogenase complex E1 inhibitors.

To identify new antifungal lead compound based on inhibitors of pyruvate dehydrogenase complex E1, a series of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives 3 were prepared and evaluated for their Escherichia coli PDHc-E1 inhibitory activity and antifungal activity. The in vitro bioassay for the PDHc-E1 inhibition indicated all the compounds exhibited significant inhibition against E. coli PDHc-E1 (IC50<21µM), special compound 3g showed the most potent inhibitory activity (IC50=4.21±0.11µM) and was demonstrated to act as a competitive inhibitor of PDHc-E1. Meanwhile, inhibitor 3g exhibited very good enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli. The assay of antifungal activity showed compounds 3e, 3g, and 3n exhibited fair to good activity against Rhizoctonia solani and Botrytis cinerea even at 12.5µg/mL. Especially compound 3n (EC50=5.4µg/mL; EC90=21.1µg/mL) exhibited almost 5.50 times inhibitory potency against B. cinerea than that of pyrimethanil (EC50=29.6µg/mL; EC90=113.4µg/mL). Therefore, in this study, compound 3n was found to be a novel lead compound for further optimization to find more potent antifungal compounds as microbial PDHc-E1 inhibitors.

Ion-abrasion scanning electron microscopy reveals surface-connected tubular conduits in HIV-infected macrophages.

HIV-1-containing internal compartments are readily detected in images of thin sections from infected cells using conventional transmission electron microscopy, but the origin, connectivity, and 3D distribution of these compartments has remained controversial. Here, we report the 3D distribution of viruses in HIV-1-infected primary human macrophages using cryo-electron tomography and ion-abrasion scanning electron microscopy (IA-SEM), a recently developed approach for nanoscale 3D imaging of whole cells. Using IA-SEM, we show the presence of an extensive network of HIV-1-containing tubular compartments in infected macrophages, with diameters of approximately 150-200 nm, and lengths of up to approximately 5 microm that extend to the cell surface from vesicular compartments that contain assembling HIV-1 virions. These types of surface-connected tubular compartments are not observed in T cells infected with the 29/31 KE Gag-matrix mutant where the virus is targeted to multi-vesicular bodies and released into the extracellular medium. IA-SEM imaging also allows visualization of large sheet-like structures that extend outward from the surfaces of macrophages, which may bend and fold back to allow continual creation of viral compartments and virion-lined channels. This potential mechanism for efficient virus trafficking between the cell surface and interior may represent a subversion of pre-existing vesicular machinery for antigen capture, processing, sequestration, and presentation.